Autophagy as a mediator of chemotherapy-induced cell death in cancer

Small Molecule Inhibition of MDM2–p53 Interaction Augments Radiation Response in Human Tumors

“…Furthermore, autophagy-related ULK-1 and DRAM genes were significantly upregulated in cells treated with AMG 232 and radiation. Although autophagy is often considered to be a cell survival mechanism, there is also evidence for the capacity of autophagy to mediate the antiproliferative and/or cytotoxic actions of selected anticancer agents (31,32). Furthermore, a direct crosstalk between apoptosis and autophagy has been identified that serves to reinforce cell death (33).…”

Median Effect Dose and Combination Index Analysis of Cytotoxic Drugs Using Flow Cytometry

“…However many of the new targeted agents interfere with constitutively active survival pathways or initiate apoptosis by directly influencing proapoptotic signals (Citri et al, 2004;Kim et al, 2005;Larsen et al, 2011;Vega et al, 2009;Zhang et al, 2009). In addition autophagic cell death and programmed necrosis are being actively investigated as alternative and pharmacologically relevant forms of programmed cell death (Berghe et al, 2010;Bijnsdorp et al, 2011;Duan et al, 2010;Gozuacik & Kimchi, 2007;McCall, 2010;Notte et al, 2011;Paglin et al, 2005;Platini et al, 2010). Combination studies should be conducted using effect biomarkers that are as close as possible to the known mechanisms targeted by single agents, and biomarkers specifically related to druginduce tumor cell death appear more adequate for the assessment of new targeted agents (Cameron et al, 2001;Facoetti et al, 2008;Wesierska-Gadek et al, 2005).…”

Development of pituitary tumor-transforming gene (PTTG) transgenic mice for the treatment of ovarian cancer.

“…Apoptosis is a highly conserved cellular program that eliminates damaged and infected cells and consists of two major pathways: the extrinsic pathway that is mediated by death receptors and the intrinsic pathway that is mediated by the mitochondria. Both pathways lead to activation of caspases, cysteine proteases that cleave different substrates and cause cellular breakdown [209]. However, more recent evidence suggests that anticancer agents also induce other forms of non-apoptotic cell death including necrosis, mitotic catastrophe, autophagy, and senescence [210][211][212].…”

“…However, more recent evidence suggests that anticancer agents also induce other forms of non-apoptotic cell death including necrosis, mitotic catastrophe, autophagy, and senescence [210][211][212]. Various anticancer chemotherapies have been shown to induce autophagy which cooperates with apoptosis to induce cell death [209,[213][214][215][216]. Autophagy enables cells to survive harsh conditions such as chemotherapy treatment and thus conferring resistance [209].…”

“…Various anticancer chemotherapies have been shown to induce autophagy which cooperates with apoptosis to induce cell death [209,[213][214][215][216]. Autophagy enables cells to survive harsh conditions such as chemotherapy treatment and thus conferring resistance [209].…”